Along with the personal devastating effects of drug abuse, there is a broad range of social consequences[unreadable] HIV/AIDS, STDs, tuberculosis, violence, crime, lost productivity and healthcare costs[unreadable]attributed to drug abuse. Arguably the most devastating consequence of drug abuse to the drug user, as well as to society, is HIV infection. The human immunodeficiency virus (HIV) leads to acquired immunodeficiency syndrome (AIDS), which can contribute to several other secondary illnesses including certain types of cancers and various fungal, bacterial and viral infections. In 2004, the National Institute on Drug Abuse reported that behavior associated with drug abuse is now the single largest factor in the spread of HIV infection in the United States. Currently, no vaccine for HIV or cure for AIDS has been identified. However, in 2003, an endogenous human enzyme apolipoprotein B editing complex 3G (APOBEC3G) was shown to attenuate HIV progression when HIV was lacking a functional viral infectivity factor (Vif) protein. Since the identification of APOBEC3G as an innate antiretroviral enzyme, numerous studies have demonstrated that the HIV Vif protein directly interacts with APOBEC3G and subsequently inhibits the antiretroviral activity of APOBEC3G. The purpose of the structural studies described herein is to understand and detail the extent of the APOBEC3G and Vif interaction; thereby, gaining invaluable insight into how to disrupt this interaction. Our structural studies described below are essential to developing a drug that can disrupt this interaction.